tbuckley/cabot-search huggingface dataset:
Biomimetic Conductive Hydrogel Scaffolds with Anisotropy and Electrical Stimulation for In Vivo Skeletal Muscle Reconstruction
Authors: Yan Xue, Jieling Li, Tianhe Jiang, Qingquan Han, Yafeng Jing, Shuo Bai, Xuehai Yan
Journal: Advanced Healthcare Materials (2023)

The nature of the hydrogel scaffold mimicking extracellular matrix plays a crucial role in tissue engineering like skeletal muscle repair. Herein, an anisotropic and conductive hydrogel scaffold is fabricated using gelatin methacryloyl (GelMA) as the matrix hydrogel and silver nanowire (AgNW) as the conductive dopant, through a directional freezing technique for muscle defect repair. The scaffold has an anisotropic structure composed of a directional longitudinal section and a honeycomb cross-section, with high mechanical strength of 10.5 kPa and excellent conductivity of 0.26 S m
Materials and Device Designs for Wireless Monitoring of Temperature and Thermal Transport Properties of Wound Beds during Healing
Authors: Hanjun Ryu, Joseph W. Song, Haiwen Luan, Youngmin Sim, Sung Soo Kwak, Hokyung Jang, Young Jin Jo, Hong‐Joon Yoon, Hyoyoung Jeong, Jaeho Shin, Do Yun Park, Kyeongha Kwon, Guillermo Antonio Ameer, John A. Rogers
Journal: Advanced Healthcare Materials (2023)

Chronic wounds represent a major health risk for diabetic patients. Regeneration of such wounds requires regular medical treatments over periods that can extend for several months or more. Schemes for monitoring the healing process can provide important feedback to the patient and caregiver. Although qualitative indicators such as malodor or fever can provide some indirect information, quantitative measurements of the wound bed have the potential to yield important insights. The work presented here introduces materials and engineering designs for a wireless system that captures spatio-temporal temperature and thermal transport information across the wound continuously throughout the healing process. Systematic experimental and computational studies establish the materials aspects and basic capabilities of this technology. In vivo studies reveal that both the temperature and the changes in this quantity offer information on wound status, with indications of initial exothermic reactions and mechanisms of scar tissue formation. Bioresorbable materials serve as the foundations for versions of this device that create possibilities for monitoring on and within the wound site, in a way that bypasses the risks of physical removal.
Extensive Phylogenomic Discordance and the Complex Evolutionary History of the Neotropical Cat Genus <i>Leopardus</i>
Authors: Jonas Lescroart, Alejandra Bonilla-Sánchez, Constanza Napolitano, Diana L Buitrago-Torres, Héctor E Ramírez-Chaves, Paola Pulido-Santacruz, William J Murphy, Hannes Svardal, Eduardo Eizirik
Journal: Molecular Biology and Evolution (2023)

Even in the genomics era, the phylogeny of Neotropical small felids comprised in the genus Leopardus remains contentious. We used whole-genome resequencing data to construct a time-calibrated consensus phylogeny of this group, quantify phylogenomic discordance, test for interspecies introgression, and assess patterns of genetic diversity and demographic history. We infer that the Leopardus radiation started in the Early Pliocene as an initial speciation burst, followed by another in its subgenus Oncifelis during the Early Pleistocene. Our findings challenge the long-held notion that ocelot (Leopardus pardalis) and margay (L. wiedii) are sister species and instead indicate that margay is most closely related to the enigmatic Andean cat (L. jacobita), whose whole-genome data are reported here for the first time. In addition, we found that the newly sampled Andean tiger cat (L. tigrinus pardinoides) population from Colombia associates closely with Central American tiger cats (L. tigrinus oncilla). Genealogical discordance was largely attributable to incomplete lineage sorting, yet was augmented by strong gene flow between ocelot and the ancestral branch of Oncifelis, as well as between Geoffroy's cat (L. geoffroyi) and southern tiger cat (L. guttulus). Contrasting demographic trajectories have led to disparate levels of current genomic diversity, with a nearly tenfold difference in heterozygosity between Andean cat and ocelot, spanning the entire range of variability found in extant felids. Our analyses improved our understanding of the speciation history and diversity patterns in this felid radiation, and highlight the benefits to phylogenomic inference of embracing the many heterogeneous signals scattered across the genome.
Intracellular Nitroreductase‐Triggered “On” and “Enhanced” Photoacoustic Signals for Sensitive Imaging of Tumor Hypoxia
Authors: Xianbao Sun, Lingling Xu, Hai‐Dong Xu, Limin Xie, Rui Wang, Zhimou Yang, Wenjun Zhan, Shurong Shen, Gaolin Liang
Journal: Advanced Healthcare Materials (2023)

Current molecular photoacoustic (PA) probes are designed with either stimulus-turned "on" or assembly-enhanced signals to trace biological analytes/events. PA probes based on the nature-derived click reaction between 2-cyano-6-aminobenzothiazole (CBT) and cysteine (Cys) (i.e., CBT-Cys click reaction) possess both "turn-on" and "enhanced" PA signals; and thus, should have higher sensitivity. Nevertheless, such PA probes, particularly those for sensitive imaging of tumor hypoxia, remain scarce. Herein, a PA probe NI-Cys(StBu)-Dap(IR780)-CBT (NI-C-CBT) is rationally designed, which after being internalized by hypoxic tumor cells, is cleaved by nitroreductase under the reduction condition to yield cyclic dimer C-CBT-Dimer to turn the PA signal "ON" and subsequently assembled into nanoparticles C-CBT-NPs with additionally enhanced PA signal ("Enhanced"). NI-C-CBT exhibits 1.7-fold "ON" and 3.2-fold overall "Enhanced" PA signals in vitro. Moreover, it provides 1.9-fold and 2.8-fold overall enhanced PA signals for tumor hypoxia imaging in HeLa cells and HeLa tumor-bearing mice, respectively. This strategy is expected to be widely applied to design more "smart" PA probes for sensitive imaging of important biological events in vivo in near future.
A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation
Authors: Chengcheng Zhang, Leilei Yu, Chenchen Ma, Shuaiming Jiang, Yufeng Zhang, Shunhe Wang, Fengwei Tian, Yuzheng Xue, Jianxin Zhao, Hao Zhang, Liming Liu, Wei Chen, Shi Huang, Jiachao Zhang, Qixiao Zhai
Journal: Cell Host & Microbe (2023)
Predicting patient outcomes after treatment with immune checkpoint blockade: A review of biomarkers derived from diverse data modalities
Authors: Yang Liu, Jennifer Altreuter, Sudheshna Bodapati, Simona Cristea, Cheryl J. Wong, Catherine J. Wu, Franziska Michor
Journal: Cell Genomics (2023)

Immune checkpoint blockade (ICB) therapy targeting cytotoxic T-lymphocyte-associated protein 4, programmed death 1, and programmed death ligand 1 has shown durable remission and clinical success across different cancer types. However, patient outcomes vary among disease indications. Studies have identified prognostic biomarkers associated with immunotherapy response and patient outcomes derived from diverse data types, including next-generation bulk and single-cell DNA, RNA, T cell and B cell receptor sequencing data, liquid biopsies, and clinical imaging. Owing to inter- and intra-tumor heterogeneity and the immune system's complexity, these biomarkers have diverse efficacy in clinical trials of ICB. Here, we review the genetic and genomic signatures and image features of ICB studies for pan-cancer applications and specific indications. We discuss the advantages and disadvantages of computational approaches for predicting immunotherapy effectiveness and patient outcomes. We also elucidate the challenges of immunotherapy prognostication and the discovery of novel immunotherapy targets.
Natural history of Ebola virus disease in rhesus monkeys shows viral variant emergence dynamics and tissue-specific host responses
Authors: Erica Normandin, Sergio Triana, Siddharth S. Raju, Tammy C.T. Lan, Kim Lagerborg, Melissa Rudy, Gordon C. Adams, Katherine C. DeRuff, James Logue, David Liu, Daniel Strebinger, Arya Rao, Katelyn S. Messer, Molly Sacks, Ricky D. Adams, Krisztina Janosko, Dylan Kotliar, Rickey Shah, Ian Crozier, John L. Rinn, Marta Melé, Anna N. Honko, Feng Zhang, Mehrtash Babadi, Jeremy Luban, Richard S. Bennett, Alex K. Shalek, Nikolaos Barkas, Aaron E. Lin, Lisa E. Hensley, Pardis C. Sabeti, Katherine J. Siddle
Journal: Cell Genomics (2023)

Ebola virus (EBOV) causes Ebola virus disease (EVD), marked by severe hemorrhagic fever; however, the mechanisms underlying the disease remain unclear. To assess the molecular basis of EVD across time, we performed RNA sequencing on 17 tissues from a natural history study of 21 rhesus monkeys, developing new methods to characterize host-pathogen dynamics. We identified alterations in host gene expression with previously unknown tissue-specific changes, including downregulation of genes related to tissue connectivity. EBOV was widely disseminated throughout the body; using a new, broadly applicable deconvolution method, we found that viral load correlated with increased monocyte presence. Patterns of viral variation between tissues differentiated primary infections from compartmentalized infections, and several variants impacted viral fitness in a EBOV/Kikwit minigenome system, suggesting that functionally significant variants can emerge during early infection. This comprehensive portrait of host-pathogen dynamics in EVD illuminates new features of pathogenesis and establishes resources to study other emerging pathogens.
Intestinal epithelial dopamine receptor signaling drives sex-specific disease exacerbation in a mouse model of multiple sclerosis
Authors: Hai-rong Peng, Jia-Qian Qiu, Qin-ming Zhou, Yu-kai Zhang, Qiao-yu Chen, Yan-qing Yin, Wen Su, Shui Yu, Ya-ting Wang, Yuping Cai, Ming-na Gu, Hao-hao Zhang, Qing-qing Sun, Gang Hu, Yi-wen Wu, Jun Liu, Sheng Chen, Zheng-Jiang Zhu, Xin-yang Song, Jia-wei Zhou
Journal: Immunity (2023)
Complete revascularization in elderly patients with myocardial infarction—a safe, effective, and necessary strategy?
Authors: Ying X. Gue, Gregory Y.H. Lip
Journal: Cell Reports Medicine (2023)

The FIRE trial compared culprit-only revascularization to physiology-guided complete revascularization strategy in elderly patients presenting with myocardial infarction. The study has shown that it is a safe approach and may confer additional prognostic benefit in patients with NSTEMI.
Non-overlapping epitopes on the gHgL-gp42 complex for the rational design of a triple-antibody cocktail against EBV infection
Authors: Junping Hong, Ling Zhong, Liqin Liu, Qian Wu, Wanlin Zhang, Kaiyun Chen, Dongmei Wei, Hui Sun, Xiang Zhou, Xinyu Zhang, Yin-Feng Kang, Yang Huang, Junyu Chen, Guosong Wang, Yan Zhou, Yanhong Chen, Qi-Sheng Feng, Hai Yu, Shaowei Li, Mu-Sheng Zeng, Yi-Xin Zeng, Miao Xu, Qingbing Zheng, Yixin Chen, Xiao Zhang, Ningshao Xia
Journal: Cell Reports Medicine (2023)

Epstein-Barr virus (EBV) is closely associated with cancer, multiple sclerosis, and post-acute coronavirus disease 2019 (COVID-19) sequelae. There are currently no approved therapeutics or vaccines against EBV. It is noteworthy that combining multiple EBV glycoproteins can elicit potent neutralizing antibodies (nAbs) against viral infection, suggesting possible synergistic effects. Here, we characterize three nAbs (anti-gp42 5E3, anti-gHgL 6H2, and anti-gHgL 10E4) targeting different glycoproteins of the gHgL-gp42 complex. Two antibody cocktails synergistically neutralize infection in B cells (5E3+6H2+10E4) and epithelial cells (6H2+10E4) in vitro. Moreover, 5E3 alone and the 5E3+6H2+10E4 cocktail confer potent in vivo protection against lethal EBV challenge in humanized mice. The cryo-EM structure of a heptatomic gHgL-gp42 immune complex reveals non-overlapping epitopes of 5E3, 6H2, and 10E4 on the gHgL-gp42 complex. Structural and functional analyses highlight different neutralization mechanisms for each of the three nAbs. In summary, our results provide insight for the rational design of therapeutics or vaccines against EBV infection.
GRP78-CAR T cell effector function against solid and brain tumors is controlled by GRP78 expression on T cells
Authors: Jorge Ibanez, Nikhil Hebbar, Unmesha Thanekar, Zhongzhen Yi, Haley Houke, Meghan Ward, Chris Nevitt, Liqing Tian, Stephen C. Mack, Heather Sheppard, Jason Chiang, M. Paulina Velasquez, Giedre Krenciute
Journal: Cell Reports Medicine (2023)

Lack of targetable antigens is a key limitation for developing successful T cell-based immunotherapies. Members of the unfolded protein response (UPR) represent ideal immunotherapy targets because the UPR regulates the ability of cancer cells to resist cell death, sustain proliferation, and metastasize. Glucose-regulated protein 78 (GRP78) is a key UPR regulator that is overexpressed and translocated to the cell surface of a wide variety of cancers in response to elevated endoplasmic reticulum (ER) stress. We show that GRP78 is highly expressed on the cell surface of multiple solid and brain tumors, making cell surface GRP78 a promising chimeric antigen receptor (CAR) T cell target. We demonstrate that GRP78-CAR T cells can recognize and kill GRP78+ brain and solid tumors in vitro and in vivo. Additionally, our findings demonstrate that GRP78 is upregulated on CAR T cells upon T cell activation; however, this expression is tumor-cell-line specific and results in heterogeneous GRP78-CAR T cell therapeutic response.
Tipping the GVH/GVL balance by targeting HIF1α
Authors: Yongxia Wu, Xue-Zhong Yu
Journal: Cell Reports Medicine (2023)

Promoting GVL activity while eliminating GVHD is the utmost goal to treat hematological malignancies with allo-HCT. Bailey et al. demonstrate that targeting HIF1α can favor GVL activity while limiting GVHD after allo-HCT even in combination with immune checkpoint inhibition.1Bailey C. Wei Y. Yan J. Huang D. Zhang P. Qi C. Lazarski C. Su J. Tang F. Wong C.S. et al.Genetic and Pharmaceutical Targeting of HIF1α allows comboimmunotherapy to boost Graft vs Leukemia effect without exacerbation Graft vs Host Disease.Cell Rep. Med. 2023; 4: 101236https://doi.org/10.1016/j.xcrm.2023.101236Abstract Full Text Full Text PDF Scopus (0) Google Scholar
Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management
Authors: Andrea I. d’Aquino, Caitlin L. Maikawa, Leslee T. Nguyen, Katie Lu, Ian A. Hall, Carolyn K. Jons, Catherine M. Kasse, Jerry Yan, Alexander N. Prossnitz, Enmian Chang, Sam W. Baker, Lars Hovgaard, Dorte B. Steensgaard, Hanne B. Andersen, Lotte Simonsen, Eric A. Appel
Journal: Cell Reports Medicine (2023)

Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management.
Cell-free multi-omics analysis reveals potential biomarkers in gastrointestinal cancer patients’ blood
Authors: Yuhuan Tao, Shaozhen Xing, Shuai Zuo, Pengfei Bao, Yunfan Jin, Yu Li, Mingyang Li, Yingchao Wu, Shanwen Chen, Xiaojuan Wang, Yumin Zhu, Ying Feng, Xiaohua Zhang, Xianbo Wang, Qiaoran Xi, Qian Lu, Pengyuan Wang, Zhi John Lu
Journal: Cell Reports Medicine (2023)

During cancer progression, tumorigenic and immune signals are spread through circulating molecules, such as cell-free DNA (cfDNA) and cell-free RNA (cfRNA) in the blood. So far, they have not been comprehensively investigated in gastrointestinal cancers. Here, we profile 4 categories of cell-free omics data from patients with colorectal cancer and patients with stomach adenocarcinoma and then assay 15 types of genomic, epigenomic, and transcriptomic variations. We find that multi-omics data are more appropriate for detection of cancer genes compared with single-omics data. In particular, cfRNAs are more sensitive and informative than cfDNAs in terms of detection rate, enriched functional pathways, etc. Moreover, we identify several peripheral immune signatures that are suppressed in patients with cancer. Specifically, we establish a γδ-T cell score and a cancer-associated-fibroblast (CAF) score, providing insights into clinical statuses like cancer stage and survival. Overall, we reveal a cell-free multi-molecular landscape that is useful for blood monitoring in personalized cancer treatment.
Aurora A kinase inhibition induces accumulation of SCLC tumor cells in mitosis with restored interferon signaling to increase response to PD-L1
Authors: Yixiang Li, Navin R. Mahadevan, Leslie Duplaquet, Deli Hong, Yavuz T. Durmaz, Kristen L. Jones, Hyeonseo Cho, Murry Morrow, Andrea Protti, Michael J. Poitras, Benjamin F. Springer, Roderick T. Bronson, Xueqian Gong, Yu-Hua Hui, Jian Du, Jackson Southard, Tran Thai, Shuqiang Li, Patrick H. Lizotte, Prafulla C. Gokhale, Quang-De Nguyen, Matthew G. Oser
Journal: Cell Reports Medicine (2023)

Despite small cell lung cancers (SCLCs) having a high mutational burden, programmed death-ligand 1 (PD-L1) immunotherapy only modestly increases survival. A subset of SCLCs that lose their ASCL1 neuroendocrine phenotype and restore innate immune signaling (termed the "inflammatory" subtype) have durable responses to PD-L1. Some SCLCs are highly sensitive to Aurora kinase inhibitors, but early-phase trials show short-lived responses, suggesting effective therapeutic combinations are needed to increase their durability. Using immunocompetent SCLC genetically engineered mouse models (GEMMs) and syngeneic xenografts, we show durable efficacy with the combination of a highly specific Aurora A kinase inhibitor (LSN3321213) and PD-L1. LSN3321213 causes accumulation of tumor cells in mitosis with lower ASCL1 expression and higher expression of interferon target genes and antigen-presentation genes mimicking the inflammatory subtype in a cell-cycle-dependent manner. These data demonstrate that inflammatory gene expression is restored in mitosis in SCLC, which can be exploited by Aurora A kinase inhibition.
An engineered immunocytokine with collagen affinity improves the tumor bioavailability, tolerability, and therapeutic efficacy of IL-2
Authors: Aliyah B. Silver, Stephany Y. Tzeng, Mallory Lager, Jeremy Wang, Jun Ishihara, Jordan J. Green, Jamie B. Spangler
Journal: Cell Reports Medicine (2023)

The clinical utility of human interleukin-2 (hIL-2) is limited by its short serum half-life, preferential activation of regulatory T (TReg) over immune effector cells, and dose-limiting toxicities. We previously engineered F10 immunocytokine (IC), an intramolecularly assembled cytokine/antibody fusion protein that linked hIL-2 to an anti-IL-2 antibody (denoted F10) that extended IL-2 half-life and augmented the immune effector to TReg ratio. Here, we leveraged molecular engineering to improve the anti-tumor therapeutic efficacy and tolerability of F10 IC by developing an iteration, denoted F10 IC-CBD (collagen binding domain), designed for intratumoral administration and in situ retention based on collagen affinity. F10 IC-CBD retained IL-2 bioactivity exclusively in the tumor and eliminated IL-2-associated toxicities. Furthermore, F10 IC exhibited potent single-agent therapeutic efficacy and synergy with systemic immune checkpoint blockade and elicited an abscopal response in mouse tumors models. This engineered fusion protein presents a prototype for the design of intratumoral therapies.
Non-invasive CT imaging biomarker to predict immunotherapy response in gastric cancer: a multicenter study
Authors: Weicai Huang, Wenjun Xiong, Lei Tang, Chuanli Chen, Qingyu Yuan, Cheng Zhang, Kangneng Zhou, Zepang Sun, Taojun Zhang, Zhen Han, Hao Feng, Xiaokun Liang, Yonghong Zhong, Haijun Deng, Lequan Yu, Yikai Xu, Wei Wang, Lin Shen, Guoxin Li, Yuming Jiang
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Despite remarkable benefits have been provided by immune checkpoint inhibitors in gastric cancer (GC), predictions of treatment response and prognosis remain unsatisfactory, making identifying biomarkers desirable. The aim of this study was to develop and validate a CT imaging biomarker to predict the immunotherapy response in patients with GC and investigate the associated immune infiltration patterns. Methods This retrospective study included 294 GC patients who received anti-PD-1/PD-L1 immunotherapy from three independent medical centers between January 2017 and April 2022. A radiomics score (RS) was developed from the intratumoral and peritumoral features on pretreatment CT images to predict immunotherapy-related progression-free survival (irPFS). The performance of the RS was evaluated by the area under the time-dependent receiver operating characteristic curve (AUC). Multivariable Cox regression analysis was performed to construct predictive nomogram of irPFS. The C-index was used to determine the performance of the nomogram. Bulk RNA sequencing of tumors from 42 patients in The Cancer Genome Atlas was used to investigate the RS-associated immune infiltration patterns. Results Overall, 89 of 294 patients (median age, 57 years (IQR 48–66 years); 171 males) had an objective response to immunotherapy. The RS included 13 CT features that yielded AUCs of 12-month irPFS of 0.787, 0.810 and 0.785 in the training, internal validation, and external validation 1 cohorts, respectively, and an AUC of 24-month irPFS of 0.805 in the external validation 2 cohort. Patients with low RS had longer irPFS in each cohort (p&lt;0.05). Multivariable Cox regression analyses showed RS is an independent prognostic factor of irPFS. The nomogram that integrated the RS and clinical characteristics showed improved performance in predicting irPFS, with C-index of 0.687–0.778 in the training and validation cohorts. The CT imaging biomarker was associated with M1 macrophage infiltration. Conclusion The findings of this prognostic study suggest that the non-invasive CT imaging biomarker can effectively predict immunotherapy outcomes in patients with GC and is associated with innate immune signaling, which can serve as a potential tool for individual treatment decisions.